Three major areas of study are proposed - studies of possible pathogenic mechanisms in SLE, therapy of SLE in humans and mice, and studies of the pathogenesis of drug-induced lupus. Studies of pathogenesis of SLE will include investigations into the role of humoral immune responses to native DNA in disease induction and perpetuation, in patients with SLE and in NZB/NZW mice. In addition, further investigations will be made into the role of defective cell-mediated immunity in patients with SLE. Therapeutic studies will include attempts to modify disease in NZB-NZW mice by inducing immune tolerance to nDNA. In addition, other NZB/NZW mice will receive treatment with various immunosuppressive agents with attention directed toward cyclophosphamide. Various dose schedules of this dru@ will be tried in an attempt to preserve therapeutic effects while avoiding oncogenic effects. A controlled trial of azathiprine in lupus patients will be continued. Studies in drug-induced LE will include a prospective study in patients receiving hydralazine to determine if lupus-like syndrome is signalled by appearance of antibodies to hydralazine and/or nDNA, and study of patients with procaineamide-induced lupus. For immune responses to procaineamide and nDNA. Overall objectives are to further identify pathogenic mechanisms in lupus and drug-induced lupus, to correlate these findings with therapeutic effrorts in order to achieve better control of the disease.